Clinical depression is a disorder characterized by low self-esteem, guilt, self-reproach, introversion, sadness, despair, sleeping disorders, eating disorders or discouragement. Depression generally causes a lower or decrease of a person's function. Anxiety is a disorder characterized by responses to anticipation of unreal or imagined danger. It manifests itself as increased heart rate, altered respiration rate, sweating, trembling, weakness, or fatigue. Psychosis is a disorder characterized by gross impairment in reality perception as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the person of the incomprehensibility of his behavior.
Major depression and anxiety occur concomitantly in more patients than either one alone. When these disorders occur together, they are associated with more severe symptoms, increased impairment of function, a longer chronic course, poorer outcome, and a higher incidence of suicide.
Antidepressants, such as venlafaxine, have been tested for the treatment of depression and symptoms of anxiety. Anti-psychotic agents, such as risperidone, are used for the treatment of psychosis. On occasion, a person suffering from depression or anxiety and psychosis will be prescribed an antidepressant agent and an anti-psychotic agent. Rather than administration of two different dosages, it would be useful in the art to have available a single dosage containing both an antidepressant and an anti-psychotic.
Venlafaxine is commercially available in an extended release capsule dosage form from Wyeth Ayerst under the trademark EFFEXOR XR™. The capsule is available in 37.5, 75, and 150 mg strengths. The capsule is disclosed in U.S. Pat. No. 4,535,186 and does not contain the venlafaxine in combination with an anti-psychotic agent. Moreover, the EFFEXOR XR™ formulation provides an incomplete release of venlafaxine.
Bymaster et al. (European Patent Application No. EP 0830864 A1) disclose a method, and compositions and dosage forms therefor, of treating psychoses with a combination of a serotonin uptake inhibitor and an anti-psychotic agent. Bymaster et al. do not disclose an osmotic device containing such combination nor the beneficial effects of sequential administration of the two drugs, one rapid release and the other controlled release, from a single dosage form.
Controlled release capsule dosage forms and osmotic device dosage forms are generally known by the skilled artisan to provide different release profiles. Effective therapy with antidepressants and anxiolytic agents is dependent upon a careful control of the blood plasma levels of these agents, and therefore, upon the release profiles of these agents from their respective dosage forms.
Osmotic devices and other tablet formulations are known for their ability to provide a controlled release of a wide range of drugs. Such osmotic devices and other tablet formulations are disclosed in U.S. Pat. No. 4,014,334 to Theeuwes et al., U.S. Pat. No. 4,576,604 to Guittard et al., Argentina Patent No. 234,493, U.S. Pat. No. 4,673,405 to Guittard et al., U.S. Pat. No. 5,558,879 to Chen et al., U.S. Pat. No. 4,810,502 to Ayer et al., U.S. Pat. No. 4,801,461 to Hamel et al., U.S. Pat. No. 5,681,584 to Savastano et al., U.S. Pat. No. 3,845,770, U.S. Pat. No. 6,004,582 to Faour et al., and Argentina Patent No. 199,301, the entire disclosures of which are hereby incorporated by reference.
These references, however, do not disclose osmotic devices that provide the specific plasma profiles or release profiles for venlafaxine (VFX), and an optional anti-psychotic agent, that the present invention provides. Moreover, the prior art does not disclose an osmotic device containing a combination of venlafaxine with an anti-psychotic agent, and generally wherein the venlafaxine and anti-psychotic agent are delivered according to specific release profiles that are advantageous over known formulations.